Noroviruses, a group of non-enveloped single-stranded RNA viruses, are the leading cause of gastroenteritis outbreaks and account for 21 million cases in the United States annually. Current prevention and control options are limited with no vaccines or therapeutics available. Antibody-based norovirus diagnostic kits suffer from low sensitivity and are dependent on the antibody used. Rapid, accurate, point-of-care diagnostic kits are critical to detect and isolate infected personnel. We propose a novel approach by using synthetic glycans as capture molecules. In this proposal, an interdisciplinary team will develop rapid, point-of-care diagnostics for the sensitive detection of norovirus. In Specific Aim 1, we will use a modular synthetic strategy to generate synthetic analogs of histo-blood group antigens and Lewis antigens, attachment factors for norovirus. In Specific Aim 2, we will develop and evaluate glycan based diagnostic platforms using panels of norovirus strains In Specific Aim 3, candidate diagnostic platforms will be compared side-by-side evaluated using clinical samples from both outbreaks and sporadic cases of gastrointestinal illness. Accomplishing the specific aims in this proposal is expected to yield rapid, robust, point of care, user friendly diagnostics for the precise and sensitive detection of all human norovirus strains. PUBLIC HEALTH RELEVANCE: An interdisciplinary team of scientists will develop glycan-based diagnostics for norovirus, a highly infectious pathogen that causes ~50% of all gastrointestinal outbreaks in the United States. We will synthesize a library of glycans, incorporate these glycans into multiple diagnostic platforms and evaluate their performance using a comprehensive panel of archived and contemporary norovirus strains. Successful completion of these specific aims is expected to lead to the development of rapid, robust, user-friendly diagnostics for different strains of norovirus.